2-Aminobenzophenones are important intermediates in the synthesis of the benzodiazephine class of pharmaceuticals as well as other products as described by Leo H. Sternbach in Angew. Chem. Int. Ed. Engl. 1971, 10, 34 and in reviews including that by David A. Walsh in Synthesis, September 1980 pp. 677-688. Benzodiazepines such as diazepam and chlordiazepoxide are useful as anxiolytics, minor tranquilizers and antagonists of gastrin and cholecystokinin for treating disorders of the gastrointestinal, central nervous and appetite regulatory systems of mammals. References to these activities include the following U.S. Patents:
______________________________________ 2,893,992 3,243,430 3,651,046 3,051,701 3,261,870 3,686,308 3,136,815 3,267,110 3,740,442 3,202,661 3,297,755 4,820,834 3,203,990 3,341,592 3,239,564 3,609,146 ______________________________________
The particular structural features of benzodiazepines which influence activity are described in the chapter "Ligand Interactions at the Benzodiazepine Receptor" by R. Ian Fryer in Comprehensive Medicinal Chemistry, pp. 539-566, Vol. 3, Ed. by John C. Emmett, Pergamon Press, Oxford (1990).
It is known that N-methoxy-N-methylamides combine with Grignard reagents and organolithium species in tetrahydrofuran to form ketones as described by Steven Nahm and Steven M. Weinreb in Tetrahedron Letter, Vol. 22, No. 39, pp. 3815-3813 (1981).
It is an object of the present invention to provide a facile high yield synthesis for 2-aminobenzophenones which is applicable with a wide variety of substituents.